Context Fluoropyrimidines constitute the backbone of chemotherapy regimens for GI tumors, including pancreatic cancer where it is used either as a radiosensitizer or as second-line after failing gemcitabine. While normal dihydropyrimidine dehydrogenase (DPD) enzyme activity is rate limiting in 5- fluorouracil (5-FU) catabolism, its deficiency could increase concentrations of bioavailable 5-FU anabolic products leading to 5-FU related toxicity syndrome. The most common toxicities include myelosuppression, stomatitis, neuropathy, and diarrhea. The prevalence of this autosommal codominently inherited pharmacogenetic syndrome is approximately 3-5% in the Caucasian population and 8% in the African-American population. Case report We present here a case of an African-American patient with pancreatic cancer who developed a desquamative skin rash on the face, trunk, and forearms as the worst rash (grade 3) following 5-FU bolus that led to the investigation of DPD enzyme. Measurement of DPD activity by radioisotopic assay methods described previously revealed an abnormally low level of 0.087 nmol/min/mg protein (reference range: 0.182-0.688 nmol/min/mg protein). She was treated toxicity with intravenous steroids and antihistamine therapy. Further 5- FU therapy was discontinued. Conclusions This case suggest that the pattern of toxicities associated with 5-FU can vary, especially in patients with different ethnic backgrounds (whites versus nonwhites). These findings become of further importance as our recent study suggests that DPD deficiency may be more common among African-Americans.
Muhammad Wasif Saif, Sandra Seller, Robert B Diasio